Symbiotic Microbes from Marine Invertebrates: Driving a New Era of Natural Product Drug Discovery

Alix Blockley,Michael Sweet,Adam Roberts,David Elliott

doi:10.3390/d9040049

Alix Blockley, Michael Sweet + Show 2 more

Open Access

https://doi.org/10.3390/d9040049

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Abstract

Invertebrates account for more than 89% of all extant organisms in the marine environment, represented by over 174,600 species (recorded to date). Such diversity is mirrored in (or more likely increased by) the microbial symbionts associated with this group and in the marine natural products (or MNPs) that they produce. Since the early 1950s over 20,000 MNPs have been discovered, including compounds produced by symbiotic bacteria, and the chemical diversity of compounds produced from marine sources has led to them being referred to as "blue gold" in the search for new drugs. For example, 80% of novel antibiotics stemming from the marine environment have come from Actinomycetes, many of which can be found associated with marine sponges, and compounds with anti-tumorigenic and anti-diabetic potential have also been isolated from marine symbionts. In fact, it has been estimated that marine sources formed the basis of over 50% of FDA-approved drugs between 1981 and 2002. In this review, we explore the diversity of marine microbial symbionts by examining their use as the producers of novel pharmaceutical actives, together with a discussion of the opportunities and constraints offered by “blue gold” drug discovery.

Highlights

The term symbiosis was first defined by the German surgeon Anton de Bary in 1878 as “the living together of differently named organisms” [1]
Due to co-evolution with their specific host, microbial symbionts express a variety of uniquely tailored biochemical traits, making them a highly productive source of secondary metabolites with well-defined architectures and medically and commercially attractive bioactivities [5]
The compounds smenamide A and B, which show potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, are likely to originate from a symbiont of another marine invertebrate

Summary

Introduction

The term symbiosis was first defined by the German surgeon Anton de Bary in 1878 as “the living together of differently named organisms” [1]. The compounds smenamide A and B, which show potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, are likely to originate from a symbiont of another marine invertebrate These compounds were isolated as a result of a detailed study into the secondary metabolites contained within the lipophilic extract of the sponge Smenospongia aurea. Further study on the same sponge species revealed two further anti-tumorigenic compounds, this time with selectivity for ovarian cancer cells These compounds, the smenothiazoles A and B (Figure 1), contained structural motifs that are present in cyanobacterial metabolites, and as such likely originate from S. spongiarum (Table 1) [49]. An isolated one, zeaenol (Figure 1), exhibited excellent fungicidal activity against the crop-pathogenic fungi Plasmopara viticola and Phytophthora infestans in a whole-plant assay (Table 1) [59]

Constraints and Future Prospects

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Conclusions